Acalabrutinib.. neutropenia and ? Once daily vs twice ?

[Catlove71]

Been on Acalabrutinib for 7 months. Was doing very well until 2 weeks ago my absolute neutrophil count went down from normal range to 0.59 , hgb up to 10.6 ( was as low as 8.5), WBC 4700, plt 158,000. I was elated with all numbers except for anc.

I was temporarily taken off Acala and received 3 shots of Nivestym. My nodes and night sweats are now increasing plus have probable food poisoning. I feel awful but no blood , no fever and improving a bit.

How long will it take for anc to rise to normal, at that point hope to go back on Acala but once a day. I am very petite so ? Twice a day was too much? Would love feedback re my pre Acala bad symptoms returning in just 5 days off of med. my FISH test showed no genetic abnormalities. Also feedback on once a day Acala.

Thank you

[lankisterguy Volunteer]

Hi Catlove71,

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There was a similar discussion yesterday here: healthunlocked.com/cllsuppo...

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And this is an area where AussieNeil has written many excellent replies

here is a list of many of the past 384 posts that mention neutropenia:

healthunlocked.com/search/p...

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Len

[Catlove71 in reply to lankisterguy]

Thank you! Glad to be a new member

[AussieNeil Partner Administrator]

Hi Catlove and welcome to our community.

Unfortunately how long it takes our bone marrow to recover is quite variable. If your bone marrow has totally stopped making neutrophils, it takes about 10 days from when it restarts making them before they grow sufficiently mature enough for release into your blood. Recovery can sometimes take longer than a few weeks. If your ANC fairly quickly jumps up to very healthy levels, then you are less likely to need shots of Nivestym (a G-CSF drug).

Your probable food poisoning will complicate understanding what's happening, but some of us do experience what's termed tumor flare when we stop taking acalabrutinib or another BTKi. Restarting the BTKi reverses the symptoms.

With respect to reducing your acalabrutinib dose, certainly some members have arranged this in discussion with their specialist, so you can certainly ask whether this is possible. Your specialist will probably first want to see your blood counts stabilise first, but perhaps they may feel that they have no option other than immediately reducing your dose in order to prevent your bone marrow from again becoming overdressed.

Neil

[Catlove71 in reply to AussieNeil]

Thank you! Glad to join many discussions in the future

[Skyshark]

Bit of a flyer to take a read across to this for 1st generation Ibrutinib, very small sample size. The first cycle at full dose was critical to remove the bulk of CLL cells after that there aren't as many left and even at lower 1/3rd doses there was enough BTKi to occupy the receptors. As the receptors are occupied it is assumed that the effectiveness is the same as at normal dose.

ashpublications.org/blood/a...

These data clearly demonstrate that the 280 or 140 mg/d dose, preceded by a cycle at the currently prescribed dose of 420 mg/d, is sufficient to bind to almost all the BTK in circulating PBMCs. It follows that the resultant reduction of free plasma ibrutinib levels could reduce the inhibition of off-target proteins.

A key issue with all dose reductions is if they became generally used on the basis of this report, or similar studies, or by taking CPY3A inhibitors to prevent the metabolism of the drug, the potential for profits from new drugs would be severely impacted and research which just might be the "cure" would dry up.